Characterization of KPC-82, a KPC-2 variant conferring resistance to ceftazidime-avibactam in a carbapenem-nonsusceptible clinical isolate of citrobacter koseri

Francois Lebreton; Brendan W. Corey; Christi L. McElheny; Alina Iovleva; Lan Preston; Katie R. Margulieux; Robert J. Cybulski; Patrick Mc Gann; Yohei Doi; Jason W. Bennett

doi:10.1128/AAC.00150-21

Characterization of KPC-82, a KPC-2 variant conferring resistance to ceftazidime-avibactam in a carbapenem-nonsusceptible clinical isolate of citrobacter koseri

Francois Lebreton^*, Brendan W. Corey, Christi L. McElheny, Alina Iovleva, Lan Preston, Katie R. Margulieux, Robert J. Cybulski, Patrick Mc Gann, Yohei Doi, Jason W. Bennett^*

^*Corresponding author for this work

Walter Reed Army Institute of Research (WRAIR)

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15 Scopus citations

Abstract

KPC-82 is a KPC-2 variant identified in a carbapenem-nonsusceptible Citrobacter koseri that confers high-level resistance to ceftazidime-avibactam. Genomic analysis revealed that bla_KPC-82 is carried by a chromosomally integrated Tn4401 transposon (disrupting porin gene phoE) and evolved by a 6-nucleotide tandem repeat duplication causing a two-amino-acid insertion (Ser-Asp) within the Ala₂₆₇-Ser₂₇₅ loop. Similar to related KPC variants, KPC-82 showed decreased carbapenemase activity when expressed in a heterologous background and remained susceptible to carbapenem/b-lactamase inhibitor combinations.

Original language	English
Article number	e00150-21
Journal	Antimicrobial Agents and Chemotherapy
Volume	65
Issue number	7
DOIs	https://doi.org/10.1128/AAC.00150-21
State	Published - Jul 2021

Keywords

CRE
Carbapenems
Ceftazidime-avibactam
Citrobacter koseri
KPC

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10.1128/AAC.00150-21

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Lebreton, F., Corey, B. W., McElheny, C. L., Iovleva, A., Preston, L., Margulieux, K. R., Cybulski, R. J., Gann, P. M., Doi, Y., & Bennett, J. W. (2021). Characterization of KPC-82, a KPC-2 variant conferring resistance to ceftazidime-avibactam in a carbapenem-nonsusceptible clinical isolate of citrobacter koseri. Antimicrobial Agents and Chemotherapy, 65(7), Article e00150-21. https://doi.org/10.1128/AAC.00150-21

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title = "Characterization of KPC-82, a KPC-2 variant conferring resistance to ceftazidime-avibactam in a carbapenem-nonsusceptible clinical isolate of citrobacter koseri",

abstract = "KPC-82 is a KPC-2 variant identified in a carbapenem-nonsusceptible Citrobacter koseri that confers high-level resistance to ceftazidime-avibactam. Genomic analysis revealed that blaKPC-82 is carried by a chromosomally integrated Tn4401 transposon (disrupting porin gene phoE) and evolved by a 6-nucleotide tandem repeat duplication causing a two-amino-acid insertion (Ser-Asp) within the Ala267-Ser275 loop. Similar to related KPC variants, KPC-82 showed decreased carbapenemase activity when expressed in a heterologous background and remained susceptible to carbapenem/b-lactamase inhibitor combinations.",

keywords = "CRE, Carbapenems, Ceftazidime-avibactam, Citrobacter koseri, KPC",

author = "Francois Lebreton and Corey, {Brendan W.} and McElheny, {Christi L.} and Alina Iovleva and Lan Preston and Margulieux, {Katie R.} and Cybulski, {Robert J.} and Gann, {Patrick Mc} and Yohei Doi and Bennett, {Jason W.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 Lebreton et al",

year = "2021",

month = jul,

doi = "10.1128/AAC.00150-21",

language = "English",

volume = "65",

journal = "Antimicrobial Agents and Chemotherapy",

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Lebreton, F, Corey, BW, McElheny, CL, Iovleva, A, Preston, L, Margulieux, KR, Cybulski, RJ, Gann, PM, Doi, Y & Bennett, JW 2021, 'Characterization of KPC-82, a KPC-2 variant conferring resistance to ceftazidime-avibactam in a carbapenem-nonsusceptible clinical isolate of citrobacter koseri', Antimicrobial Agents and Chemotherapy, vol. 65, no. 7, e00150-21. https://doi.org/10.1128/AAC.00150-21

Characterization of KPC-82, a KPC-2 variant conferring resistance to ceftazidime-avibactam in a carbapenem-nonsusceptible clinical isolate of citrobacter koseri. / Lebreton, Francois; Corey, Brendan W.; McElheny, Christi L. et al.
In: Antimicrobial Agents and Chemotherapy, Vol. 65, No. 7, e00150-21, 07.2021.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Characterization of KPC-82, a KPC-2 variant conferring resistance to ceftazidime-avibactam in a carbapenem-nonsusceptible clinical isolate of citrobacter koseri

AU - Lebreton, Francois

AU - Corey, Brendan W.

AU - McElheny, Christi L.

AU - Iovleva, Alina

AU - Preston, Lan

AU - Margulieux, Katie R.

AU - Cybulski, Robert J.

AU - Gann, Patrick Mc

AU - Doi, Yohei

AU - Bennett, Jason W.

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AB - KPC-82 is a KPC-2 variant identified in a carbapenem-nonsusceptible Citrobacter koseri that confers high-level resistance to ceftazidime-avibactam. Genomic analysis revealed that blaKPC-82 is carried by a chromosomally integrated Tn4401 transposon (disrupting porin gene phoE) and evolved by a 6-nucleotide tandem repeat duplication causing a two-amino-acid insertion (Ser-Asp) within the Ala267-Ser275 loop. Similar to related KPC variants, KPC-82 showed decreased carbapenemase activity when expressed in a heterologous background and remained susceptible to carbapenem/b-lactamase inhibitor combinations.

KW - CRE

KW - Carbapenems

KW - Ceftazidime-avibactam

KW - Citrobacter koseri

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VL - 65

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

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M1 - e00150-21

ER -

Characterization of KPC-82, a KPC-2 variant conferring resistance to ceftazidime-avibactam in a carbapenem-nonsusceptible clinical isolate of citrobacter koseri

Abstract

Keywords

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